Loss of LRP1 in Adult Neural Stem Cells Impairs Migration to Ischemic Lesions

After ischemia, cells in the brain parenchyma upregulate stromal derived factor 1 (SDF1), driving chemokine receptor CXCR4-mediated migration of adult neural stem cells to the ischemic injury. We discovered a novel regulator of CXCR4 in neural stem cells, low-density lipoprotein receptor related protein 1 (LRP1). We used Nestin-driven knockout of LRP1 and induction of td-tomato in neural stem cells of adult mice. We observed reduced localization of td-tomato positive cells to the lesion, and find disrupted CXCR4-mediated neural stem cell migration in vitro, which is likely driven by LRP1-mediated loss of CXCR4 expression in vivo. Our results suggest that LRP1 is a novel regulator of CXCR4 in neural stem cells. This heretofore unknown interaction between LRP1 and CXCR4 could have significant consequences for multiple aspects of neural stem cell physiology.

Automated summary

After ischemia, SDF1 upregulates in brain parenchyma cells, promoting the migration of adult neural stem cells to the injury site through the CXCR4 receptor. We identified LRP1 as a novel regulator of CXCR4 in neural stem cells and observed disrupted neural stem cell migration in vitro and reduced localization to the lesion in LRP1 knockout mice. Our findings suggest that the interaction between LRP1 and CXCR4 could have significant implications for neural stem cell physiology.